Previous studies have demonstrated the close association of an impaired synaptic (Na plus K) pump in vitro with electrocorticographic seizures in vivo. Active Na ion outflux and K ion influx were profoundly decreased within synaptosomes isolated from primary and secondary epileptogenic foci of cold lesions. In contrast, no alterations in active K ion influx were observed, in "normal" controls, in electroshock convulsions and in non-seizure generating cold lesions. To strengthen the thesis that an impaired (Na plus K) pump within synaptic terminals is involved in seizure generation we now propose: (A) to assess glial and microsomal combination of synaptosomes isolated from epileptogenic cold lesions by assaying carbonic anhydrase and NADPH-cytochrome C reductase activities; (B) to contrast synaptosomal sodium outflux in non-seizure generating cold lesions from those of seizure generating cold lesions; (C) to differentiate the effects of focal neuronal firing from effects of maximal electroshock convulsions and from events associated with seizure generation. Sodium and potassium transport will be studied in synaptosomes isolated from brain regions subjected to local electrical stimulation. To understand mechanisms responsible for the low pump flux of Na and K within synaptic terminals of seizure foci, we also propose to study in "normal" controls, electrically stimulated brains, epileptogenic cold lesions and non-epileptogenic cold lesions: (A) The kinetic properties of ouabain sensitive Na and K transport within synaptosomes under varying ionic conditions; (B) the kinetic characteristics of Na ion K ion ATPase and its ouabain sensitive fraction and (C) H3 ouabain binding within synaptic terminals as an index of the number of (Na plus K) pump sites. Such studies should indicate whether qualitative changes in individual pump sites or a reduction in the number of pump units is responsible for the low pump flux of ions observed in seizure foci.